Ischemic stroke remains a major health problem associated with high mortality and severe morbidity. In spite of the extensive research in the field of stroke biology, there is little effective treatment for a completed disease onset. Numerous neuroprotective strategies have failed in clinical trials because of lack of efficacy or unacceptable side-effects. The challenge of clinical trial design is now to understand the process leading to ischemic brain injury and thus identify the targets for intervention in stroke. Therefore, uncovering cellular and molecular processes involved in ischemic brain injury is of critical importance. The review discusses the current understanding of these processes engaged in pathogenesis of stroke including excitotoxicity and inflammation. In addition recruitment of endogenous progenitors engaged in neurogenesis and vascular regeneration has been implicated. All of the aforementioned changes opted for therapeutic intervention to protect neurons in the region adjacent to the ischemic cerebral tissue and enhance cell recovery. Stem cell transplantation seems to offer a major promise of this therapy in stroke disorders.